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Association of ABCG2 rs2231142 Allele and BMI With Hyperuricemia in an East Asian Population.

ABSTRACT: Objectives: Genetic variants and obesity are risk factors for hyperuricemia (HUA). Recent genome-wide association studies have identified ABCG2 rs2231142 as one of the most prominent genetic variants for HUA in an East Asian population. Nevertheless, no large-scale studies have demonstrated any interactive effects between this variant and obesity on serum urate level in Asians. This study aimed to determine the interaction of ABCG2 rs2231142 variant and body mass index (BMI) and its effect on risk of HUA in an East Asian population. Methods: The study was conducted using the Taiwan Biobank database, a population-based biomedical research database of patients with Taiwanese Han Chinese ancestry aged 30-70years between September 2014 and May 2017. Detailed physical information on participants were collected by questionnaires and genotyping using Affymetrix TWB 650K SNP chip. The primary outcome was HUA, defined as a serum uric acid level>7.0mg/dl. Odds ratio (OR) of HUA was analyzed using logistic regression models and the effects of interaction between ABCG2 rs2231142 variants and BMI on serum uric acid level were explored. Results: We identified 25,245 subjects, 4,228 (16.75%) of whom had HUA. The prevalence of HUA was 30% in men and 3.8% in women. The risk of HUA was significantly associated with ABCG2 rs2231142 risk T allele, with more HUA in TT genotype (OR: 2.40, 95% CI: 2.11-2.72, p<0.001) and TG genotype (OR: 1.64, 95% CI: 1.51-1.78, p<0.001) in men, and TT genotype (OR: 2.42, 95% CI: 1.83-3.20, p<0.001) and TG genotype (OR: 1.82, 95% CI: 1.46-2.23, p<0.001) in women, compared with their counterparts. Moreover, we found a strong genetic-environmental interaction associated with the risk of HUA. There was increased risk of HUA by the interaction of ABCG2 rs2231142 variant and BMI for TT genotype (OR: 7.42, 95% CI: 2.54-21.7, p<0.001) and TG genotype (OR: 4.25, 95% CI: 2.13-8.47, p<0.001) in men compared with the GG genotype in men, and for TT genotype (OR: 25.43, 95% CI: 3.75-172.41, p<0.001) and TG genotype (OR: 3.05, 95% CI: 0.79-11.71, p=0.011) in women compared with the GG genotype in women. Conclusion: The risk of HUA was markedly increased by the interaction of ABCG2 rs2231142 variant and BMI, both in men and in women. Body weight control and reduction in BMI are recommended in high-risk patients with the ABCG2 rs2231142 risk T allele.

SUBMITTER: Chen YJ

PROVIDER: S-EPMC8438144 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:The ABCG2 rs2231142 single nucleotide polymorphism (SNP) is one of the most significant genetic variants associated with hyperuricemia (HUA) in Asian populations. However, the risk of ABCG2 rs2231142 variants for HUA could interact with other important HUA risk variants and cardiovascular factors. This study investigated the effects of the combined association among ABCG2 rs2231142 and multiple HUA genetic variants or cardiovascular risk factors on HUA risk and serum uric acid (sUA) levels in an elderly Chinese population. METHODS:A total of 1206 participants over 65?years old were enrolled in this study. Physical and laboratory examinations were performed for all participants. The ABCG2 rs2231142, SLC2A9 rs3733591, and SLC22A12 rs893006 SNPs were assayed using a standardized protocol. Logistic regression analysis and liner regression were adjusted respectively to account for the association between ABCG2 rs2231142 and other genetic variants, as well as between cardiovascular risk factors and HUA risk and sUA levels. RESULTS:The prevalence of HUA was 14.71% in the elderly community-dwelling population. The ABCG2 rs2231142 risk T allele was associated with HUA risk (odds ratio (OR)?=?1.63, 95% confidence interval (CI): 1.27-2.11; p?=?1.65?×?10-?4) and with increased sUA levels (Beta?=?0.16, p?=?6.75?×?10-?9) in the whole study population. Linear regression analysis showed that the mean sUA level increased linearly with the number of risk alleles of the three candidate genetic variants (Beta?=?0.18, p?=?1.94?×?10-?12) The joint effect of the ABCG2 rs2231142 T allele and cardiovascular risk factors (obesity, hypertension and dyslipidemia) was also associated with increased HUA risk and sUA levels. Each copy of the risk T allele was significantly associated with enhanced HUA risk in patients with hypertriglyceridemia (OR?=?2.52, 95% CI: 1.33-4.60; p?=?0.003) compared to controls. CONCLUSION:Our findings reinforce the importance of the ABCG2 rs2231143 variant as a crucial genetic locus for HUA in Chinese populations and demonstrated the combined effects of multiple genetic risk variants and cardiovascular risk exposures on HUA risk and increased sUA level.

Project description:BackgroundAlthough there has been a well-established association between overweight-obesity and hypertension, whether such associations are heterogeneous for South Asian populations, or for different socioeconomic groups is not well-known. We explored the associations of overweight and obesity using South Asian cut-offs with hypertension, and also examined the relationships between body mass index (BMI) and hypertension in various socioeconomic subgroups.MethodsWe analysed the recent Demographic and Health Survey (DHS) data from Bangladesh, India, and Nepal, with a total of 821,040 men and women. Hypertension was defined by 2017 ACC/AHA cut-offs and by Joint National Committee 7 (JNC7) cut-offs for measured blood pressure and overweight and obesity were defined by measured height and weight. We used multiple logistic regressions to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) of hypertension for overweight and obesity as well as for each 5-unit increase in BMI.ResultsThe prevalence of hypertension using JNC7 cut-offs among participants increased by age in all three countries. The prevalence ranged from 17.4% in 35-44 years to 34.9% in ≥55 years in Bangladesh, from 4.6% in 18-24 years to 28.6% in 45-54 years in India, and from 3.8% in 18-24 years to 39.2% in ≥55 years in Nepal. Men were more likely to be hypertensive than women in India and Nepal, but not in Bangladesh. Overweight and obesity using both WHO and South Asian cut-offs were associated with higher odds of hypertension in all countries. For each 5 kg/m2 increase in BMI, the ORs for hypertension were 1.79 (95% CI: 1.65-1.93), 1.59 (95% CI: 1.58-1.61), and 2.03 (95% CI: 1.90-2.16) in Bangladesh, India, and Nepal, respectively. The associations between BMI and hypertension were consistent across various subgroups defined by sex, age, urbanicity, educational attainment and household's wealth index.ConclusionsOur study shows that the association of BMI with hypertension is stronger for South Asian populations at even lower cut-offs points for overweight and obesity. Therefore, public health measures to reduce population-level reduction in BMI in all population groups would also help in lowering the burden of hypertension.

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Association of ABCG2 rs2231142 Allele and BMI With Hyperuricemia in an East Asian Population.

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